Chronic pain is a debilitating condition with significant medical and socioeconomic implications. Patients with chronic pain often require multi-modality treatment including medications. Several categories of medications are currently used in chronic pain management, including non-steroidal anti- inflammatory drugs, acetaminophen, opioids, antidepressants, antiepileptic drugs such as gabapentinoids, and topical agents. The concept of combination drug therapy has been known for several decades, which refers to the combined use of different categories of medications in order to achieve improved pain relief as a primary goal. While opioids are strong analgesics for the treatment of moderate to severe pain, their use is often complicated by side effects and sometimes adverse outcomes such as addiction and paradoxical opioid-induced hyperalgesia (OIH), particularly when used for chronic pain management. Although it is uncommon for clinicians to use opioids as a single drug treatment for chronic pain, few clinical trials have adequately assessed whether 1) opioid analgesia could be improved by adding a non-opioid adjunct such as antidepressant and 2) overall opioid use in a combination drug therapy would be decreased as compared to a respective single drug therapy. This unique HHS funding opportunity (PAR-14-225: Clinical Evaluation of Adjuncts to Opioid Therapies for the Treatment of Chronic Pain) is both timely and clinically relevant, which helps fill a knowledge gap on this important clinical issue. In this application, we propose to conduct a double-blind, randomized, and placebo-controlled clinical study in order to examine whether duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid analgesia and reduce overall opioid use. We will recruit subjects with chronic (? 3 months) neck or back radicular pain symptoms to participate in a 10-week study, who are currently experiencing unsatisfactory pain relief [visual analog score (VAS): ? 5/10] despite on non-opioid treatment for at least three months. Primary study outcomes will be 1) changes in VAS pain score and 2) overall and rescue opioid use during the study. Secondary outcomes will include 1) side effect profile, 2) dropout rate, 3) functional status, 4) opioid dependece, 5) OIH, and 6) urine drug screening. Methodologically, we will use both clinical (VAS; questionnaries) and experimental (quantitative sensory testing) pain assessment tools. In addition, we will develop a plan to make the study outcome data available to clinicians who manage opioid therapies such as primary care physicians and nurse practitioners in both acedemic and community hospitals. We expect that this study will yield important data on the effectiveness, or lack thereof, of adding an adjunct to opioid therapy in chronic pain management. Positive outomes will help improve the overall effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.